Orthodontic Treatment-Induced Periodontal, Microbiological, and Local Inflammatory Changes: A Systematic Review and Meta-Analysis

Background/Objectives: Orthodontic treatment induces controlled mechanical forces that alter the periodontal environment, including changes in oral microbiota composition and activation of local inflammatory pathways. Despite the widespread and growing use of orthodontic appliances across all age groups, the magnitude, timing, and multi-domain biological impact of these changes have not been comprehensively quantified in a single systematic synthesis. This systematic review and meta-analysis aimed to synthesize the available evidence on periodontal clinical parameters, oral microbiota composition, and local inflammatory biomarkers associated with orthodontic treatment using fixed appliances and clear aligners, and to provide a structured, GRADE-rated evidence base for clinical practice. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to March 2026. Prospective cohort studies, longitudinal clinical studies, and randomized controlled trials evaluating periodontal parameters, oral microbiota, and inflammatory biomarkers during orthodontic treatment were included. Quantitative synthesis was performed using mean differences or standardized mean differences with 95% confidence intervals, primarily assessing within-group (pre–post) changes. Results: Eighteen studies (n = 812 patients; follow-up 3–12 months) met inclusion criteria. Fixed orthodontic appliances were consistently associated with transient increases in plaque index (MD 0.45, 95% CI 0.32–0.58; I2 = 62%), gingival index (MD 0.38, 95% CI 0.25–0.51; I2 = 55%), and bleeding on probing (MD 15.2%, 95% CI 10.1–20.3%; I2 = 48%), particularly during early treatment phases. Microbiological analyses demonstrated within-group shifts toward increased prevalence of periodontopathogenic species (Streptococcus mutans OR 2.45, 95% CI 1.89–3.18; Porphyromonas spp. OR 2.14, 95% CI 1.67–2.75) in patients treated with fixed appliances. Local inflammatory responses were characterized by elevated IL-1β (MD 1.2, 95% CI 0.8–1.6) and IL-6 (MD 0.9, 95% CI 0.6–1.2) in gingival crevicular fluid. Certainty of evidence was rated moderate for plaque and gingival indices and low for microbiological and inflammatory outcomes (GRADE). Conclusions: Orthodontic treatment—particularly with fixed appliances—is associated with transient, reversible deterioration of periodontal indices, shifts toward a more dysbiotic oral microbiome, and elevation of local inflammatory mediators in gingival crevicular fluid during active treatment phases. These changes are manageable through structured preventive protocols and regular periodontal monitoring. Future prospective studies with concurrent control groups and standardized multi-domain outcome measures are needed to better define the magnitude and reversibility of these biological responses. PROSPERO: CRD420261336117.